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Antidepressant Paxil—Warnings

There have been 41 drug regulatory agency warnings on Paxil from seven countries (United States, United Kingdom, Canada, Japan, Australia, New Zealand, and Germany) and the European Union. These are as follows:

United States, December 14, 2011: The FDA notified healthcare professionals and the public about the use of selective serotonin reuptake inhibitor (SSRI) antidepressants, including Paxil, by women during pregnancy and the potential risk of a rare heart and lung condition known as Persistent Pulmonary Hypertension of the Newborn (PPHN). Source: “Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants: Drug Safety Communication – Use During Pregnancy and Potential Risk of Persistent Pulmonary Hypertension of the Newborn” FDA, December 14, 2011, http://www.fda.gov/drugs/drugsafety/ucm283375.htm.

United States, July 26, 2011: The FDA issued a warning about serious central nervous system (CNS) reactions that occur when the antibacterial drug linezolid (Zyvox) is given to patients taking psychiatric medications that work through the serotonin system of the brain (such a Paxil). Some of the reactions included Serotonin Syndrome a potentially (a life threatening drug reaction that causes the body to have too much serotonin), trouble with coordination, muscle twitching, etc. There were also some deaths reported. Source: Zyvox (linexolid), MedWatch Safety Information, July 26, 2011.

Australia, February 2011: The Australian Therapeutic Goods Administration reported in their safety bulletin that a recent study suggested a higher death rate amongst women taking tamoxifen for breast cancer who were also using the antidepressant Paroxetine (Paxil). Prescribers need to take caution to when prescribing antidepressants to women taking tamoxifen. Source: “Drug interaction between tamoxifen and antidepressants,” Medicines Safety Update, No. 1, 2011.

New Zealand, September 2010: MedSafe issued information in their Prescriber Update publication about the use of antidepressants during pregnancy. The Medicines Adverse Reactions Committee (after reviewing studies on two types of antidepressants – SSRIs and SNRIs) concluded that there is a small increased risk of heart birth defects associated with fluoxetine (Prozac), similar to that seen with Paroxetine (Paxil). Also, there is a possibility of this increased risk for all SSRIs or SNRIs antidepressants (not just Paxil and Prozac). In addition to the risk of birth defects, SSRIs and SNRIs antidepressants have been associated with an increase in risk of pre-term birth, persistent pulmonary hypertension (little or no blood flow into an infants lungs after birth) and newborn withdrawal symptoms. Source: “The use of antidepressants in pregnancy,” Prescriber Update, MedSafe, Vol. 31, No. 3, September 2010.

Australia, October 2008: The Australian Adverse Drug Reaction Bulletin published a report called “Drug-induced Hyponatraemia” (low sodium levels in the blood). One of the main drugs suspected as causing hyponatraemia adverse reactions are antidepressants, including Paxil. The Bulletin warned that there have been many reports of this side effect to the Australian Therapeutic Goods Administration. Source: “Drug-induced Hyponatraemia,” Australian Adverse Drug Reaction Bulletin, Vol. 27, No. 5, October 2008.

United Kingdom, February 05, 2008: UK’s Medicines and Healthcare products Regulatory Agency ordered drug companies to update the warnings on antidepressants, such as Paxil, to show that they cause suicidal thoughts and behavior. Source: “Implementation of warnings on suicidal thought and behaviour in antidepressants,” Medicines and Healthcare Products Regulatory Agency, February 5, 2008.

European Union, January 2008: The Pharmacovigilance Working Party (a party that provides advice on the safety of medicinal products and on the investigation of adverse reactions associated with medicinal products authorized in the European Union) recommended an update to product labeling and all antidepressants (including Paxil) patient information leaflets to include information on the increased risk of suicide for children to young adults. Source: “Antidepressants and suicidal thoughts and behaviour,” Pharmacovigilance Working Party, January 2006.

United States, May 02, 2007: The FDA officially extended the age group covered in the October 15, 2004 black box warning regarding antidepressants (including Paxil) causing suicidal tendencies in children and adolescents, to include 18 to 24 year-olds. Source: “FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications,” FDA News, May 2, 2007.

United States, July 19, 2006: The FDA warned of the risk of a fatal lung condition in newborns whose mothers took newer antidepressants, such as Paxil, during pregnancy. The agency added it was seeking more information about persistent pulmonary hypertension (a heart and lung disorder) in newborns from the drugs. It asked drug makers to list the potential risk on their drug labels. Source: Susan Heavey, “U.S. FDA warns of new antidepressant risks,” Reuters, July 19, 2006.

Japan, June 14, 2006: Japan’s Health Ministry ordered GlaxoSmithKline to change its package insert for Paxil to add the warning that the drug can cause suicidal behavior in young adults and that patients should be observed carefully when it is prescribed to them. According to the Health Ministry, clinical tests conducted in foreign countries showed that 11 out of 3,455 people (0.32%) who were taking Paxil attempted suicide. On the other hand, only 1 of 1,978 people (0.05%) who were taking placebo attempted suicide. Suicidal actions were often shown amongst 18-30 year-olds. Source: “Danger of increasing attempt of suicide: The Health Ministry calls for attention on Paxil,” Shimotsuke Newspaper, June 14, 2006.

United States, May 12, 2006: GlaxoSmithKline and the U.S. FDA warned doctors that the antidepressant Paxil increased the risk of suicide in young adults. Source: “Paxil (Paroxetine hydrochloride) Tablets and Oral Suspension” FDA MedWatch, May 12, 2006.

United States, May 09, 2006: GlaxoSmithKline issued a change to the Clinical Worsening and Suicide Risk section of the drug literature for Paxil and Paxil CR. GlaxoSmithKline’s research showed a higher frequency of suicidal behavior in adults ages 18-24 taking the drug. 2.19% of people showed suicidal behavior who were taking the drug versus only .92% in people taking a placebo. Source: John E. Kraus, “Important Prescribing Information,” GlaxoSmithKline, May 9, 2006.

Germany, May 08, 2006: The German Drug Regulatory Agency (BfArM) issued risk information on the newer antidepressant Paroxetine (Paxil), that it increased the risk of cardiac malformation in newborns when the mother took Paroxetine (Paxil) during her pregnancy. All German drug manufacturers producing Paroxetine drugs were ordered to implement the warning and safety notes on their drug information leaflets. Source: “Questions and answers on Paroxetine,” Risk information of the BfArM, May 8, 2006.

Canada, December 16, 2005: Health Canada issued Important Safety Information on Paxil, publishing GlaxoSmithKline’s letter to healthcare professionals about a Swedish study that had found heart malformations in newborns of mothers taking Paxil during their first trimester. “Due to the potential for discontinuation symptoms, doctors should inform patients that the drug should not be stopped without first discussing it with their doctor,” the letter further states. Source: “New Safety Information Regarding Paroxetine: Second Large Study Shows an Increased Risk of Cardiac Defects, Over Other Antidepressants, Following First Trimester Exposure to Paroxetine” Health Canada, December 16, 2005.

United States, December 08, 2005: The FDA issued a Public Health Advisory that warned physicians about the potential risk to the fetus if they prescribed Paxil to pregnant women in their first trimester. The drug may cause birth defects, including heart malformations. Source: “FDA Public Health Advisory Paroxetine” Food and Drug Administration (FDA), December 8, 2005.

Canada, September 29, 2005: GlaxoSmithKline, after discussions with Health Canada, issued a letter to healthcare professionals advising of a change to their prescribing information stating that Paxil is associated with an increase of birth defects when used by pregnant women. Source: “Important Prescribing Information,” GlaxoSmithKline, September 2005.

United States, September 27, 2005: The FDA and GlaxoSmithKline issued a warning that showed a recent study the drug company conducted on 3,581 pregnant women taking Paxil or other antidepressants during their first trimester of pregnancy. They found an increased risk of major congenital (present at birth) and cardiovascular (heart) malformations at birth for those mothers taking Paxil. The most common defect was malformations between the heart’s two main pumping chambers. Paxil’s website also said, “Babies born to mothers who have taken antidepressants, including newer ones such as Paxil, in the third trimester of pregnancy have reported complications, including difficulties with breathing, turning blue, seizures, changing body temperature, feeding problems, vomiting, low blood sugar, floppiness, stiffness, shakiness, irritability or constant crying…There have also been reports of premature births in pregnant women exposed to SSRIs [newer antidepressants], including Paxil.” Source: Miranda Hitti, “New Study Links Paxil to Twice as Many Birth Defects as Other Antidepressants” WebMD, September 27, 2005.

Australia, September 07, 2005: The Australian Therapeutics Goods Administration issued an information sheet to health professionals warning that use of newer antidepressants—especially Paxil—in early pregnancy could cause congenital heart abnormalities in newborns. It reported that Danish researchers had determined an association in the first trimester of pregnancy. Source: “General information concerning use of SSRI antidepressants in pregnant women” Australian Government, Department of Health and Ageing September 7, 2005.

European Union, August 19, 2005: The Commission of the European Communities, representing 25 European countries, endorsed and issued the strongest warning yet against child antidepressant use (which includes Paxil) as recommended by Europe’s Committee for Medicinal Products for Human Use (CHMP). Clinical trials had shown that the drugs caused suicidal behavior including suicide attempts and suicidal ideation, aggression, hostility (predominantly aggression, oppositional behavior and anger) and/or related behavior. Source: Commission of the European Communities Commission Decision concerning the placement on the market, under Article 21 of the Directive 2001/83/EC of the European Parliament and of the Council, Brussels 19-VIII-2005, C (2205) 3256.

Australia, August 04, 2005: The Australian Therapeutic Goods Administration published an Adverse Drug Reactions Bulletin that reported on a review of newer antidepressants (such as Paxil) which found evidence supporting an association between them and “new onset of suicidality” in adults. It usually developed shortly after beginning the drugs or after an increase in dosage that could cause akathisia (body restlessness), agitation, nervousness and anxiety. Similar symptoms could also occur during withdrawal. Source: “Suicidality with SSRIs: adults and children,” The Australian Therapeutic Goods Administration, Adverse Drug Reactions Bulletin, Vol. 24, No. 4, p. 14, August 2005.

Canada, July 28, 2005: Health Canada issued a release from GlaxoSmithKline (GSK) who, after discussions with Health Canada, issued new safety information regarding the newer antidepressant Paxil (Paroxetine) and Paxil CR. It must not be administered together with Orap (pimozide), an older antipsychotic drug, because it increases the level of Orap in the blood. This may result in arrhythmia (irregular heartbeats) that can sometimes be serious and even life-threatening. GSK sent a letter to health care professionals informing them of this information. Source: “Subject: Important New Safety Information for the Use of Paxil and Paxil CR in patients taking pimozide,” Health Canada, issuing GSK release, July 28, 2005.

United States, June 30, 2005: The FDA issued a Public Health Advisory entitled “Suicidality in Adults Being Treated with Antidepressant Medications,” that stated that several recent scientific publications suggested the possibility of an increased risk of suicidal behavior in adults taking both older and newer antidepressants (which includes Paxil). It recommended that physicians monitor adults who took antidepressants for suicidal tendencies. Source: “Suicidality in Adults Being Treated with Antidepressant Medications,” FDA Public Health Advisory, June 30, 2004.

European Union, April 25, 2005: The European Medicines Agency’s Committee for Medicinal Products for Human Use concluded that antidepressants (like Paxil) were associated with increased suicide-related behavior and hostility in young people. The London-based watchdog said it recommended the inclusion of strong warnings across the whole of the European Union to doctors and parents about these risks and that the drugs should not be used in children and adolescents in off label situations. Source: “EU calls for tougher warnings on antidepressants for kids” News-Medical.net, April 25, 2005.

United States, October 15, 2004: The FDA ordered pharmaceutical companies to add a “black box” warning to antidepressant packaging (including Paxil), explaining that the drugs could cause suicidal thoughts and actions in children and teenagers. It also directed the manufacturers to print and distribute medication guides with every antidepressant prescription and to inform patients of the risks. Source: “Suicidality in Children and Adolescents Being Treated With Antidepressant Medications,” FDA Public Health Advisory, October 15, 2004.

Canada, June 03, 2004: Health Canada issued an advisory to the public that stated stronger warnings have been placed on antidepressants. These warnings indicate that people taking these drugs at any age are at greater risk of behavioral or emotional changes including self-harm or harm to others. The advisory said, “A small number of patients taking drugs of this type may feel worse instead of better…. For example, they may experience unusual feelings of agitation, hostility or anxiety, or have impulsive or disturbing thoughts that could involve self-harm or harm to others.” The drugs mentioned in this Advisory are Wellbutrin (bupropion), Zyban (bupropion), Celexa (citalopram), Prozac (fluoxetine), Luvox (fluvoxamine), Remeron (mirtazapine), Paxil (Paroxetine), Zoloft (sertraline), Effexor (venlafaxine). Source: Jirina Vlk, “Health Canada advises Canadians of stronger warnings for SSRIs and other newer anti-depressants,” Health Canada, 2004-31, June 3, 2004.

European Union, April 22, 2004: The European Agency for the Evaluation of Medicinal Products issued a press release that reported that, according to clinical trials, Paroxetine (Paxil)-containing medicines could cause suicidal behavior and hostility in children. It recommended that Paroxetine not be used in children and recommended that young adults be observed carefully for signs and symptoms of suicidal behavior or hostility. Paroxetine was shown to have little effectiveness in children according to clinical trials. The committee also recommended strengthened warnings on the withdrawal symptoms of Paroxetine, which are common. Source: “European Agency for the Evaluation of Medicinal Products: Committee for Proprietary Medicinal Products 20-22 April 2004” EMEA, The European Agency for the Evaluation of Medicinal Products, Press Release April 2004.

United States, March 22, 2004: The FDA asked drug companies to add new warnings on 10 widely used antidepressants. It said patients who used Prozac (fluoxetine), Zoloft (sertraline), Paxil (Paroxetine), Luvox (fluvoxamine), Celexa (citalopram), Lexapro (escitalopram), Wellbutrin (bupropion), Effexor (venlafaxine), Serzone (nefazodone), and Remeron (mirtazapine), should be closely monitored for possible suicidal behavior and anxiety, especially when the patient first begins taking the drugs or changes doses. It stated, “Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia [severe restlessness], hypomania [abnormal excitement, mild mania] and mania [psychosis characterized by exalted feelings, delusions of grandeur and overproduction of ideas], have been reported in adult and pediatric patients being treated with antidepressants.” Source: “Worsening Depression and Suicidality in Patients Being Treated with Antidepressant Medications,” FDA Public Health Advisory, March 22, 2004.

Canada, February 03, 2004: Health Canada issued a warning to the public about Prozac, Paxil, Celexa, Luvox, Remeron, Zoloft and Effexor. The warning states that reports show an increased risk of suicide in children taking these drugs. Health Canada said its action was based on international studies that linked the use of these drugs to “suicide-related events,” suicides and suicide attempts. Source: “Health Canada advises Canadians under the age of 18 to consult physicians if they are being treated with newer anti-depressants”, About Health Canada, February 2004.

United States, October 27, 2003: The FDA released a “Health Advisory” where they announced that they had completed a preliminary review of reports of suicidality in pediatric patients for eight antidepressant drugs (both newer and older antidepressants, including Paxil) and had determined that additional data and analysis and public discussion of available data were needed on the issue. The Health Advisory simply urged health care professionals to use the drugs with caution. Source: Food and Drug Administration (FDA), “Reports of Suicidality in Pediatric Patients Being Treated with Antidepressant Medications for Major Depressive Disorder (MDD)” October 27, 2003.

Ireland, October 01, 2003: The Irish Medicines Board (IMB) announced that, based on the findings of recent Seroxat (Paxil) studies by GlaxoSmithKline, the drug was not effective in children and adolescents with “major depressive disorder” and showed an increased rate of self-harm and potentially suicidal behavior in this age group. The IMB considered that Seroxat should not be prescribed to people under 18. Source: Irish Medicines Board, “Seroxat (Paroxetine) Contraindicated For Children” October 06, 2003.

Australia, August 01, 2003: The Australian Therapeutic Goods Administration reported that the use of newer antidepressants, like Paxil, during or after pregnancy may result in adverse reactions to newborn babies, due to the withdrawal effect following intra-uterine exposure, or a toxic effect from ingestion of an antidepressant in breast-milk.The withdrawal effects the baby experienced included agitation, jitteriness, poor feeding, sleepiness/lethargy, gastrointestinal symptoms and hypotania (deficient tone or tension). Source: “Maternal SSRI Use and Neonatal Effects,” The Australian Therapeutic Goods Administration, Adverse Drug Reactions Bulletin, Vol 22, No. August 4, 2003, p. 14.

Canada, July 01, 2003: Health Canada’s Health Products and Food Branch warned health care professionals, “Until further information is available, Paxil should not be used in… pediatric patients… due to a possible increased risk of suicide-related adverse events in this patient population.” Further, incidents of suicidal thoughts and self-harm were nearly twice as high on Paxil as on placebo (5.3% vs. 2.8%). Source: Health Canada, “Important Drug Safety Information” Health Products and Food Branch, July 2003.

United States, June 19, 2003: The U.S. FDA issued a statement that it was reviewing reports of increased risk of suicidal thinking and suicide attempts in children and adolescents using Paxil. The FDA noted that following the review of the same data, the UK department of health issued a press release saying that Paxil must not be used to treat depression in children and adolescents under the age of 18. Source: “FDA Statement Regarding the Anti-Depressant Paxil for Pediatric Population,” U.S. Food and Drug Administration, FDA Talk Paper, June 19, 2003.

United Kingdom, June 18, 2003: GlaxoSmithKline issued a warning to British physicians against the use of Paxil in children, acknowledging failure of clinical trials to “demonstrate efficacy in major depressive disorders and doubling the rate of reported adverse events—including suicidal thoughts and suicide attempts—compared to placebo.” Source: Evelyn Pringle, “TeenScreen–Normal Kids Labeled Mentally Ill,” OpEdNews, August 1, 2006.

United Kingdom, June 10, 2003: UK’s Medicines and Healthcare products Regulatory Agency (MHRA), warned that “Seroxat [Paxil] must not be used to treat depression in children and teenagers under the age of 18.” The Department of Health stated, “It has become clear that the benefits of Seroxat [Paxil] in children, for the treatment of depressive illness, do not outweigh these risks.” MHRA states that Seroxat is associated with an increased risk of self-harm and suicidal behavior and thoughts in people under the age of 18. Source: Department of Health “Seroxat Must Not Be Used For Treatment Of Children” Press Release R1191 – 12 Press Officer: Alison Langley, June 10, 2003.